RESUMEN
BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder in women that necessitates effective and safe treatment alternatives. This study aimed to evaluate the therapeutic efficacy of Vitex negundo seed in a letrozole-induced PCOS rat model. RESULTS: Findings of the present study demonstrated that administration of hydro-ethanolic extract of Vitex negundo (VNE) effectively restored endocrino-metabolic imbalances associated with PCOS, along with correction of antioxidant enzymes level, proinflammatory cytokines, and apoptotic bio-markers. LC-MS analysis confirmed the presence of cinnamic acid, plumbagin and nigundin B as the prominent phytochemicals in VNE. The observed beneficial effects could be attributed to the active compounds in Vitex negundo extract, which exhibited hypoglycemic, hypolipidemic, and catabolic effects on body weight. Additionally, the extract contributed to hormonal balance regulation by modulating the steroidogenic enzymes, specifically by tuning gonadotropins level and correcting the LH:FSH ratio, through the modulation of ERα signalling and downregulation of NR3C4 expression. The antioxidant properties of phytochemicals in Vitex negundo seed were apparent through the correction of SOD and catalase activity. While it's anti-inflammatory and antiapoptotic action were associated with the regulation of mRNA expression of TNF-α, IL-6, BAX, Bcl2. Molecular docking study further indicated the molecular interaction of above mentioned active phytocompounds of VNE with ERα, NR3C4 and with TNFα that plays a critical mechanistic gateway to the regulation of hormone signalling as well as synchronizing the inflammation cascade. Furthermore, the histomorphological improvement of the ovaries supported the ameliorative action of Vitex negundo extract in the letrozole-induced PCOS model. CONCLUSIONS: This study indicates the potential of Vitex negundo seed as a multifaceted therapeutic option for PCOS. VNE offers a holistic strategy for PCOS with antiandrogenic, anti-inflammatory, and antioxidant properties, driven by its major compounds like cinnamic acid, plumbagine, and nigundin B.
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Cinamatos , Síndrome del Ovario Poliquístico , Vitex , Humanos , Ratas , Femenino , Animales , Síndrome del Ovario Poliquístico/inducido químicamente , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Letrozol/uso terapéutico , Vitex/química , Receptor alfa de Estrógeno , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Simulación del Acoplamiento Molecular , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/química , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Factor de Necrosis Tumoral alfa , SemillasRESUMEN
The adverse effects of arsenic-chelating drugs make it essential to replace invasive chelating therapy with non-invasive oral therapy for arsenic poisoning. The goal of the current investigation was to determine whether the uterine damage caused by arsenization could be repaired by the n-butanol fraction of Moringa oleifera seed (NB). The rats were orally administered with arsenic (10 mg/kg BW) for the initial 8 days, followed by NB (50 mg/kg) for the next 8 days without arsenic. The probable existence of different components in NB was evaluated by HPLC-MS. Pro and anti-inflammatory indicators were assessed by RT-PCR and western blot. ESR-α was detected via immunostaining. Arsenic-exposed rats had significantly increased lipid peroxidation and decreased antioxidant enzyme activity, which were markedly reduced after NB treatment. Weaker ESR-α expression and distorted uterine histomorphology following arsenication were retrieved significantly by NB. Meaningful restoration by NB was also achieved for altered mRNA and protein expression of various inflammatory and apoptotic indicators. Molecular interaction predicted that glucomoringin and methyl glucosinolate of moringa interact with the catalytic site of caspase-3 in a way that limits its activity. However, NB was successful in restoring the arsenic-mediated uterine hypofunction. The glucomoringin and methyl glucosinolate present in n-butanol fraction may play a critical role in limiting apoptotic event in the arsenicated uterus.
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Arsénico , Moringa oleifera , Moringa , Femenino , Ratas , Animales , Arsénico/toxicidad , Estrés Oxidativo , 1-Butanol , Glucosinolatos/farmacología , Antioxidantes/metabolismo , Moringa oleifera/metabolismo , Extractos Vegetales/farmacología , Semillas/metabolismoRESUMEN
BACKGROUND: Chronic fluoride toxicity induces oxidative strain and lipid peroxidation and imparts deleterious effects on human metabolic organs. AIM: The present study aimed to expose the defensive impact of ferulic acid against sodium fluoride (NaF) induced hepatorenal dysfunction at the biochemical and antioxidative systems. METHODS: In-vivo. Rats were arbitrarily separated into five groups as control, sodium fluoride-treated (200 ppm kg -1), vitamin C -as a positive control, and FA co-administered groups with 10 mg kg -1 and 20 mg kg -1 body weight for 56 days. In the present investigation, we measured antioxidant enzymes, superoxide dismutase, catalase, and lactate dehydrogenase by electrozymographic and spectrophotometric methods. Biochemical assessment of TBARS, conjugated diene, and different serum biomarkers was done for liver and kidney functionality tests. In-silico. An in-silico study was conducted through a molecular docking experiment to evaluate the binding potentiality of FA by employing AutoDock Vina [version 1.5.6] to overcome the abnormality in the activities of catalase, and superoxide dismutase in NaF promoted toxicity of hepatorenal system. In-vitro. An in vitro biochemical experiment was conducted to support the in-silico study. RESULTS: Superoxide dismutase and catalase were decreased in the intoxicated rat. Ferulic acid (FA) as an antioxidant remarkably defended the NaF-mediated deterioration of the antioxidative status in the hepatorenal system, lowering lipid peroxidation products, malondialdehyde, and conjugated diene. Serum biomarkers, ALT, AST, ALP, urea, and creatinine increased in the intoxicated group than in control. Ferulic acid significantly neutralized the ill effects of NaF on serum lipid profile. In-silico analysis hypothesized the strong interaction of FA with the active side of catalase and superoxide dismutase that prevented the binding of NaF at the active site of these mentioned enzymes and this was further validated by in-vitro assay. CONCLUSION: However, FA modulates free radical generation and protected these metabolic organs against sodium fluoride-induced injury.
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Antioxidantes , Fluoruros , Humanos , Ratas , Animales , Antioxidantes/metabolismo , Catalasa/metabolismo , Fluoruros/farmacología , Fluoruro de Sodio/farmacología , Simulación del Acoplamiento Molecular , Glutatión/metabolismo , Ratas Wistar , Estrés Oxidativo , Hígado/metabolismo , Superóxido Dismutasa/metabolismo , Biomarcadores/metabolismo , Peroxidación de LípidoRESUMEN
The present study represented an innovative strategy for inactivating the secreted invasins (lignocellulolytic enzymes) of fungal phytopathogens using natural phytochemicals to combat fungal infection to the pulses. A fungal pathogen (Aspergillus niger SKP1) was isolated from the white lentil (Vigna mungo), which has the ability to synthesize different lignocellulolytic enzymes. An in silico docking study elucidated that quercetin, naringin, epigallocatechin gallate, curcumin, and cinnamic acid were the prime efficient phytochemicals to inhibit the activity of fungal invasive enzymes like endoglucanase, endo-1,4-ß-xylanase, and glucoamylase. Considering this observation, extracted phytochemicals in different mixtures were applied to prevent growth of the isolated pathogen under in situ experimental studies. The minimal inhibitory concentrations (MIC50) and minimal fungicidal concentration (MFC50) values of the first mixture (naringenin, epicatechin gallate, and cinnamic acid) and second mixture (quercetin and curcumin) were 170 and 220 mg/L and 320 and 380 mg/L, respectively. The studied phytochemicals were established to be cytosafe when compared to the commercial fungicides. The seeds of the white lentil were subjected to 1 year of long-term storage with the two aforementioned combinatorial phytochemicals. Subsequent morphological and physiological analyses revealed the complete protection of the stored seeds from the fungal infection. The present work has enough potentiality for the storage of pulses using natural preservatives that circumvent the adverse effect of the chemical preservatives on the ecosystem.
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Curcumina , Quercetina , Aspergillus niger , Curcumina/farmacología , Ecosistema , Fitoquímicos/farmacología , Quercetina/farmacologíaRESUMEN
The non-invasive treatment strategy is indispensable to overcome the side effects of conventional treatment with chelating agents against arsenic. Presence of catechins and flavonoids in Camellia sinensis have potential antioxidant properties and other beneficial effects. The aim of the study was to explore the curative potential role of Camellia sinensis against uterine damages produced by sodium arsenite in mature albino rats. A dose of 10 mg of Camellia sinensis ethyl acetate (CS-EA) fraction/100 gm body weight was provided to the sodium arsenite-treated rats (10 mg/Kg body weight). LC-MS analysis was used for the detection of active component in CS-EA fraction. Enzymatic antioxidants analysis carried out by reproducible native gel technique. Hormones and some pro and anti-inflammatory markers were detected by ELISA, PCR, and western blot techniques respectively. Immunostaining was performed for the detection of estradiol receptor alpha. LC-MS analysis of CS-EA fraction ensured the presence of active tea polyphenol and tea catechin of which highest peak of epigallocatechin-3 gallate (EGCG) was obtained in this study. Significant elevations of lipid peroxidation end products followed by the diminution of antioxidant enzymes activities were noted in arsenicated rats which were capably retrieved by the treatment of CS-EA fraction. Post-treatment with CS-EA fraction meaningfully improved gonadotrophins and estradiol signalling in association with a highly expressing estradiol receptor-α (ERα) in the ovary and uterus followed by the maintenance of normal utero-ovarian histoarchitecture in arsenic fed rats. CS-EA fractioned treated group overturned the sodium arsenite driven higher expression of pro-inflammatory cytokines and proapoptotic markers along with a low level of anti apoptotic Bcl-2 expression and comparatively lower NF-κB signalling in the uterus via regulating IKK ß kinase mostly by EGCG of CS-EA fraction. However, ethyl acetate fraction of Camellia sinensis played a critical role in minimizing arsenic-mediated uterine hypo-function.
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Arsénico , Camellia sinensis , Acetatos , Animales , Antioxidantes , Arsénico/análisis , Femenino , FN-kappa B/genética , Estrés Oxidativo , Ratas , Ratas Wistar , Té , Útero , Proteína X Asociada a bcl-2RESUMEN
An oral painless dietary therapy is also indispensable in the management of arsenic toxicity despite of its conventional painful therapeutic management. The present study focused on the management of arsenic mediated female reproductive dysfunctions by dietary therapy of N-acetyl cysteine (NAC). Here, sodium arsenite was given at the dose of 10 mg/kg body weight orally for the first 8 day. Day 9 onwards up to day 16 these arsenicated rats were provided with NAC (250 mg/kg body weight) enriched basal diet once daily. Arsenic intoxicated group exhibited a comparable inactivation of antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) due to oxidative stress in reproductive organs along with a simultaneous elevation of lipid peroxidation state and decline in non-protein soluble thiols (NPSH) level in female reproductive organs. Arsenic intoxication also accomplished with the up-regulation of inflammatory markers tumour necrosis factor (TNF α) and nuclear factor κB (NF κB). Pro-apoptotic Bax gene and p53 gene expressions were also raised due to arsenic intoxication while anti-apoptotic Bcl-2 gene expression was suppressed. In fact, arsenication decreased the circulating level of vitamin B12 and folic acid. Dietary NAC supplementation significantly reversed back the activity of antioxidant enzymes in arsenite fed rats towards normalcy and also sustained the normal reproductive cyclicity, utero-ovarian histo-morphology and estradiol receptor α (ER-α) expression in these reproductive organs. Dietary NAC exerted its positive action against arsenic intoxication by up-regulation of Bcl-2 gene expression along with the suppression of pro-apoptotic Bax gene and p53 gene. Thus, dietary NAC also plays anti-apoptotic, anti-inflammatory, and anti-oxidative role against arsenic toxicity. NAC also regulates the components (vitamin B12 and folic acid) of S-adenosylmethionine pool in the way of probable removal of arsenic from the system.
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Acetilcisteína/uso terapéutico , Antiinflamatorios/uso terapéutico , Apoptosis/efectos de los fármacos , Arsenitos/toxicidad , Expresión Génica/efectos de los fármacos , Ovario/efectos de los fármacos , Útero/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Apoptosis/genética , Suplementos Dietéticos , Femenino , Masculino , Ovario/metabolismo , Ovario/patología , Ovario/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Útero/metabolismo , Útero/patología , Útero/fisiopatologíaRESUMEN
The painful invasive chelation therapy makes it challenging to continue the prolonged treatment against arsenic toxicity. Hence, the significance of the present preliminary investigation was to explore a noninvasive treatment strategy against sodium arsenite (As3+) by the use of a hydroethanolic extract of Moringa oleifera (MO) seed. Arsenic treatment (10 mg/kg body-weight) in animals showed significant level of oxidative stress as evidenced by increased serum levels of malondialdehyde (MDA), conjugated dienes (CD) and reduced level of non-protein thiol (NPSH). A significant diminution in the activities of enzymatic antioxidants was noted in As3+-treated rats. As3+ treatment showed a lengthy phase of metestrous in animals followed by significantly diminished ovarian steroidogenesis, increased ovarian follicular degeneration and distortion of uterine tissue histomorphology. In addition, there was a significant depletion of Vitamin-B9 (folate) and B12 following As3+ ingestion. The levels of circulating TNF-α, homocysteine (Hcy), uterine-IL-6, and liver metallothionein (MT-1) were significantly elevated in arsenic treated rats. MO at a dose of 100 mg/kg body-weight could successfully mitigate the uterine ROS generation by maintaining the uterine antioxidant status in As3+- treated rats. This seed extract prevented the deterioration of As3+-mediated ovarian-steroidogenesis and ovarian and uterine histoarchitecture significantly. B9 and B12 levels were also improved following the ingestion of the MO extract in arsenicated animals. Elevation of Hcy, TNF-α and IL-6 was also prevented by this MO seed extract in As3+-treated rats. A further increase of MT-1 level was achieved after MO ingestion in As3+-treated rats. Here, the alleviation of arsenic toxicity might involve via the regulation of the components of S-adenosine methionine (SAM) pool and MT-1.
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Arsenitos/toxicidad , Moringa oleifera/química , Extractos Vegetales/farmacología , Compuestos de Sodio/toxicidad , Útero/efectos de los fármacos , Administración Oral , Animales , Antioxidantes/metabolismo , Femenino , Homocisteína/metabolismo , Metalotioneína/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Ratas , Ratas Wistar , Semillas , Útero/patología , Complejo Vitamínico B/metabolismoRESUMEN
Background Curcumin is extensively used as a therapeutic intervention for treating several ailments. The antioxidant curcumin has an anti-inflammatory and chelating property with arsenic to exhibit a strong therapeutic effect on reproductive organs. This study was undertaken to describe the protective effect of noninvasive administration of curcumin against sodium-arsenite-mediated uterine hazards in female Wistar rats. Methods Twenty-four female Wistar rats were randomly divided into four groups. The treatment was continued for 8 days and given orally sodium arsenite (10 mg/kg body weight) in combination with curcumin (20 mg/kg body weight). Results Our evaluation revealed that 8 days of sodium arsenite (10 mg/kg body weight) treatment reduced the activities of the uterine enzymatic antioxidants superoxide dismutase, catalase, and peroxidase. Blood levels of vitamin B12 and folic acid decreased followed by an increased serum lactate dehydrogenase, homocysteine level, and hepatic metallothionein-1 in arsenic-treated rats. Necrosis of uterine tissue along with the disruption of ovarian steroidogenesis was marked in arsenic-treated rats with an upregulation of uterine NF-κB and IL-6 along with a raised level of serum TNF-α. Oral administration of curcumin (20 mg/kg body weight/day) in arsenic-treated rats significantly reinstated these alterations of the antioxidant system followed by an improvement of ovarian steroidogenesis and the circulating level of B12 and folate along with the downregulation of serum homocysteine, metallothionein-1, and cytokines. Conclusions The findings of this study clearly and strongly elucidated that arsenic-induced oxidative stress in uterus is linked to an alteration of inflammation-signaling biomarkers and these have been protected through the co-administration of curcumin due to its anti-inflammatory, free radical scavenging, and antioxidant activity by the possible regulation of an S-adenosine methionine pool.
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Arsénico/administración & dosificación , Curcumina/efectos adversos , Citocinas/metabolismo , Inflamación/metabolismo , Metalotioneína/metabolismo , Útero/efectos de los fármacos , Animales , Antioxidantes/farmacología , Arsenitos/efectos adversos , Catalasa/metabolismo , Femenino , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Compuestos de Sodio/efectos adversos , Superóxido Dismutasa/metabolismo , Útero/metabolismoRESUMEN
This investigation explored a dietary therapy of pectic polysaccharide (CCPS) (2â¯mg/ Kg BW) against female repro-toxicity and infertility triggered by sodium arsenite (As3+) (10 mg/ Kg BW) in Wistar rats. The isolated CCPS consists of D-galactose and D-methyl galacturonate with a molar ratio of 1: 4. FTIR spectral analysis of CCPS and CCPS- sodium arsenite (As3+) complex indicated a possible chelating property of CCPS in presence of binding sites (OH-/COOH) for As3+. Series of negatively charged galacturonate residues in CCPS provide better potential for cation chelation. CCPS significantly mitigated As3+ induced ovarian, uterine lipid peroxidation, and reactive oxygen species (ROS) generation by the restoration of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities. CCPS post-treatment enhanced ovarian steroidogenesis along with a restoration of normal tissue histoarchitecture in As3+ fed rats by regulating the estradiol receptor alpha (ER-α). CCPS suppressed anti-inflammatory properties effectively found since a down-regulation of NF-kappa B (NF-ÒB), pro-inflammatory tumor necrosis-α (TNF-α) and interleukin-6 (IL-6) were observed in arsenicated rats with CCPS. This study confirmed the up-regulation of uterine pro-apoptotic/ apoptotic proteins caspase-3, poly ADP ribose polymerase (PARP), proliferating cell nuclear antigen (PCNA), phospho p53 and Bax, followed by down-regulation of Bcl-2 and protein Kinase B (AKT) signaling pathway along with uterine tissue regeneration in As3+ exposed rats. Oral CCPS attenuated the above apoptotic expressional changes significantly and dietary CCPS ensured successful fertility with the birth of healthy pups in lieu of infertile condition in As3+ fed rats. Moreover, this study also supports that CCPS treatment attenuated the As3+ toxicity by modulating the S-adenosine methionine (SAM) pool components, B12, folate and homocysteine.
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Antiinflamatorios/uso terapéutico , Apoptosis/efectos de los fármacos , Infertilidad Femenina/tratamiento farmacológico , Momordica charantia/química , Pectinas/uso terapéutico , Animales , Antiinflamatorios/aislamiento & purificación , Arsenitos , Catalasa/metabolismo , Femenino , Expresión Génica/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Infertilidad Femenina/inducido químicamente , Masculino , Ovario/patología , Estrés Oxidativo/efectos de los fármacos , Pectinas/aislamiento & purificación , Embarazo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Compuestos de Sodio , Superóxido Dismutasa/metabolismo , Útero/patologíaRESUMEN
Managing arsenic intoxication with conventional metal chelators is a global challenge. The present study demonstrated the therapeutic role of probiotics against arsenic-induced oxidative stress and female reproductive dysfunction. Sodium arsenite-treated (1.0 mg/100 g body weight) Wistar female rats were followed up by a post-treatment of commercially available probiotic mixture in powder form (0.25 mg/100 g body weight) orally. Rats that experienced arsenic ingestion showed a significant lessening in the activities of uterine superoxide dismutase (SOD), catalase activities, and the level of non-protein soluble thiol (NPSH) with a concomitant increase in malondialdehyde (MDA) and conjugated dienes (CD). Exposure to arsenic significantly lowered the levels of vitamin B12 and estradiol. Exposure to arsenic highly expressed the inflammatory marker and transcription factor NF-κB. Arsenic-mediated instability of these above parameters was controlled by the probiotics with a rebuilding of better function of anti-oxidant components. Besides its function in regulating endogenous anti-oxidant system, probiotics were able to augment the protection against mutagenic uterine DNA-breakage, necrosis, and ovarian-uterine tissue damages in arsenicated rats.
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Arsenitos/farmacología , L-Lactato Deshidrogenasa/sangre , FN-kappa B/fisiología , Probióticos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Compuestos de Sodio/farmacología , Útero/metabolismo , Vitamina B 12/sangre , Animales , Daño del ADN , Estradiol/sangre , Femenino , Peroxidación de Lípido , Ratas , Superóxido Dismutasa/metabolismoRESUMEN
Lipid peroxidation and ROS generation are the pathogenesis of chronic fluoride toxicity, and its detrimental effects on human reproduction are noted drastically. The aim of the present study was to elucidate the defensive effects of soy protein concentrate (SPC) against sodium fluoride (NaF)-induced uterine dysfunction at biochemical and histological level. Rats were randomly distributed into four groups as control, NaF-treated (200 ppm), and SPC co-administered groups (20 mg and 40 mg/ 100 g body weight) for 16 days. SPC reversed the toxic effects of NaF. SPC significantly ameliorated the NaF-induced alterations of the antioxidant system in the uterus by decreasing lipid peroxidation products and by increasing antioxidant activities. SPC significantly counteracted the adverse effects of NaF on serum level of lactate dehydrogenase (LDH) and inflammatory markers Interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and nuclear factor kappa-B (NF-κB). Our results also explored that lipid profile was meaningfully altered due to NaF and also focused a diminution of circulating homocysteine (Hcy) and altered lipid profiles along with a diminished quantity of serum B12 and B9. However, both the doses of SPC reverted back serum levels of B12, B9, and Hcy status in similar fashion along with its corrective action on lipid profile. NaF-treated group exhibited a marked degree of reduction in the weights of ovary and uterus with an alteration of normal tissue histology and significant diminution in serum estradiol (ES) levels without fluctuating uterine estradiol receptor-α (ER-α). However, SPC restored the normal tissue histoarchitecture and also increased the functional efficiency and expression of the ER-α receptor by overturning the ES levels in NaF-treated rats. Moreover, both the doses of SPC were effective against NaF-induced alterations, although 40 mg SPC/100 g body weight had better efficacy in ameliorating the NaF-induced adverse effects on the uterus and ovary.
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Homocisteína/metabolismo , Ovario/efectos de los fármacos , Fluoruro de Sodio/toxicidad , Proteínas de Soja/farmacología , Útero/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Peso Corporal/efectos de los fármacos , Receptor alfa de Estrógeno/metabolismo , Femenino , Humanos , Hiperlipidemias/inducido químicamente , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/metabolismo , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Peroxidación de Lípido/efectos de los fármacos , Ovario/metabolismo , Ovario/patología , Ratas Wistar , Útero/metabolismo , Útero/patologíaRESUMEN
Arsenic consumption through drinking water is a worldwide major health problem. Management of arsenic intoxication with invasive, painful therapy using metal chelators is usually used as a conventional treatment strategy in human. In this present study, we examined the efficacy of oral administration of N-acetyl l-cysteine (NAC) in limiting arsenic-mediated female reproductive disorders and oxidative stress in female Wistar rats. The treatment was continued for 8â¯days (2 estrus cycles) on rats with sodium arsenite (10â¯mg/Kg body weight) orally. We examined the electrozymographic imprint of three different enzymatic antioxidants in uterine tissue. Rats fed with sodium arsenite exhibited a significant lessening in the activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx). Uterine DNA breakage, necrosis, ovarian and uterine tissue damage, disruption in steroidogenesis were also found in arsenic treated rats. Co-administration of NAC at different doses (50â¯mg/kg body weight, 100â¯mg/kg body weight, respectively) significantly reversed the action of uterine oxidative stress markers like malondialdehyde (MDA), conjugated dienes (CD) and non protein soluble thiol (NPSH); and noticeably improved antioxidant status of the arsenic fed rats. This ultimately resulted in the uterine tissue repairing followed by improvement of ovarian steroidogenesis. However, this effective function of NAC might be crucial for the restoration of arsenic-induced female reproductive organ damage in rats.
RESUMEN
Continuation of prolonged treatment against arsenicosis with conventional chelating therapy is a global challenge. The present study was intended to evaluate the defensive effect of arjunolic acid against arsenic-induced oxidative stress and female reproductive dysfunction. Wistar strain adult female rats were given sodium arsenite (10 mg/kg body weight) in combination with arjunolic acid (10 mg/kg body weight) orally for two estrous cycles. Electrozymographic analysis explored that arjunolic acid co-treatment counteracted As3+-induced ROS production in uterine tissue by stimulating the activities of endogenous enzymatic antioxidants. Arjunolic acid was able to enhance the protection against mutagenic uterine DNA breakage, necrosis, and ovarian-uterine tissue damages in arsenicated rats by improving the ovarian steroidogenesis. The mechanisms might be coupled with the augmentation of antioxidant defense system, partly through the elimination of arsenic with the involvement of S-adenosyl methionine pool where circulating levels of vitamin B12, folic acid, and homocysteine play critical roles as evidenced from our present investigation.
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Arsénico/toxicidad , Ácido Fólico/sangre , Estrés Oxidativo/efectos de los fármacos , Triterpenos/farmacología , Útero/efectos de los fármacos , Vitamina B 12/sangre , Animales , Intoxicación por Arsénico/metabolismo , Intoxicación por Arsénico/prevención & control , Femenino , Ovario/efectos de los fármacos , Ovario/metabolismo , Ratas Wistar , Esteroides/biosíntesis , Útero/metabolismoRESUMEN
Momordica charantia (MC) fruit known as bitter gourd, is of potential nutritional and medicinal value. The objectives of the present in vitro study were to evaluate the efficacy of bioactive pectic polysaccharides (CCPS) of MC along with another well-known bioactive compound curcumin in the abrogation of hepatocellular oxidative stress persuaded by sodium arsenite. Electrozymographic method was developed for the assessment of superoxide dismutase (SOD) and catalase activities of liver tissues maintained under an in vitro system. A significant association of CCPS of MC in combination with curcumin was found in the alleviation of oxidative stress induced by sodium arsenite in liver slice. Generated data pointed out that CCPS of MC and curcumin separately or in combination can offer significant protection against alterations in malondialdehyde (MDA), conjugated diene (CD) and antioxidative defense (SOD, CAT) markers. Furthermore, results of hepatic cell DNA degradation strongly supported that both these co-administrations have efficacy in preventing cellular damage. This is the first information of extracted polysaccharides from MC preventing arsenic induced damage in a liver slice of rat.
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This study experimentally assessed bacterial water-to-air partitioning coefficients resulting from showerhead aerosolization of water contaminated with Brevundimonas diminuta or Pseudomonas aeruginosa, and estimated human exposure through inhalation. Dechlorinated tap water was spiked with two cell densities (109 and 1010 CFU l-1) and cycled at three temperatures (10, 25, and 37 or 40ºC) through a full-scale shower system. For reproducibility, spiked water concentrations were intentionally higher than found in natural environments. Three types of samplers measured size distribution and viable concentrations throughout the system. Results indicate low levels of respirable bioaerosols were generated. The ratio of bacterial contaminant that was effectively aerosolized (bacterial water-to-air partitioning coefficient, PC bwa ) was low - averaging 1.13×10-5 L m-3 for B. diminuta and 8.31×10-6 L m-3 for P. aeruginosa. However, the respirable fraction of aerosolized organisms was high, averaging above 94% (in shower) and above 99% (downstream) for both organisms. This study found no significant difference in bioaerosol load for a forward facing versus reverse facing individual. Further, for the average hot shower (33-43°C) the total number of respirable bioaerosols is higher, but the observed culturability of those aerosolized cells is lower when compared to lower temperatures. Bacterial water to air partitioning coefficients were calculated to predict microbial air concentration and these empirical parameters may be used for assessing inhalation as a route of exposure to pathogens in contaminated waters.
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BACKGROUND: Head and neck cancer (HNC) surgery is associated with high intraoperative blood loss which may require urgent blood transfusion. Many strategies have been recommended to decrease the need for allogenic transfusion. Use of perioperative tranexamic acid (TA) has a promising role. AIMS: This study was to evaluate the effectiveness of single preoperative bolus dose of TA on blood loss prevention and red blood cell transfusion in patients undergoing HNC surgery. STUDY DESIGN: A prospective, double-blind, and randomized controlled study. MATERIALS AND METHODS: From 2007 July to 2010 January; 80 patients, aged (35-55), of American Society of Anesthesiologists II-III scheduled for unilateral HNC surgeries were randomly received either TA (Group T) in a dose of 20 mg/kg diluted to 25 cc with normal saline or an equivalent volume of normal saline (Group C) in a tertiary care hospital. Hemoglobin (Hb) concentration, platelet count, packed cell volume, fibrinogen level, D-dimer level were measured pre- and post-operatively. RESULTS: Saline (C) Group required more blood, colloid, crystalloid for blood loss. In Group T, 32 patients did not require transfusion of any blood products compared to five patients in Group C (P < 0.0001) and only eight units of blood was transfused in Group T, whereas a total of 42 units of blood was transfused in Group C. Even after numerous transfusions, Hb% after 6 h and 24 h in Group C were significantly low in comparison with Group T (P < 0.05). CONCLUSION: Thus, TA significantly reduces blood loss and chances of colloid, blood, and crystalloid transfusion caused by HNC surgery.
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BACKGROUND: Misoprostol is very effective in cervical ripening and is used for termination of pregnancy. A similar effect on the nonpregnant uterus will facilitate gynecological operations, and hence we assessed the effect of misoprostol on the nonpregnant uterus of premenopausal women. MATERIALS AND METHODS: In a prospective double-blinded randomized controlled trial, 280 women were randomly allocated into two groups (12 women did not complete the intervention). Study (A) and control (B) group received 400 µg of misoprostol or 400 mg of metronidazole tablets (as a placebo) respectively in the posterior vaginal wall 6 h prior to gynecological procedures. RESULTS: The mean cervical dilatation was significantly higher (P < 0.0001) in misoprostol compared to placebo group (4.6 ± 0.96 mm vs. 3.6 ± 0.82 mm), benefit were also observed on secondary outcome measures which were need for further dilatation, time taken for further dilatation, ease of dilatation, subjective assessment of pain by visual analog scale. Only 3.61% patients complained of intolerable pain during dilatation in the study group while in control group 48.74% complained of intolerable pain and required anesthesia. Most common side effects of misoprostol were abdominal pain and mild vaginal bleeding. CONCLUSION: Misoprostol was effective in cervical ripening of nonpregnant premenopausal uterus to facilitate gynecological procedures.
RESUMEN
Arsenic is a grade I human carcinogen. It acts by disrupting one-carbon (1C) metabolism and cellular methyl (-CH3) pool. The -CH3 group helps in arsenic disposition and detoxification of the biological systems. Vitamin B12 and folate, the key promoters of 1C metabolism were tested recently (daily 0.07 and 4.0 µg, respectively/100 g b.w. of rat for 28 days) to evaluate their combined efficacy in the protection from mutagenic DNA-breakage and tissue damages. The selected tissues like intestine (first-pass site), liver (major xenobiotic metabolizer) and lung (major arsenic accumulator) were collected from arsenic-ingested (0.6 ppm/same schedule) female rats. The hemo-toxicity and liver and kidney functions were monitored. Our earlier studies on arsenic-exposed humans can correlate carcinogenesis with DNA damage. Here, we demonstrate that the supplementation of physiological/therapeutic dose of vitamin B12 and folate protected the rodents significantly from arsenic-induced DNA damage (DNA fragmentation and comet assay) and hepatic and renal tissue degeneration (histo-architecture, HE staining). The level of arsenic-induced free-radical products (TBARS and conjugated diene) was significantly declined by the restored actions of several antioxidants viz. urate, thiol, catalase, xanthine oxidase, lactoperoxidase, and superoxide dismutase in the tissues of vitamin-supplemented group. The alkaline phosphatase, transaminases, urea and creatinine (hepatic and kidney toxicity marker), and lactate dehydrogenase (tissue degeneration marker) were significantly impaired in the arsenic-fed group. But a significant protection was evident in the vitamin-supplemented group. In conclusion, the combined action of folate and B12 results in the restitution in the 1C metabolic pathway and cellular methyl pool. The cumulative outcome from the enhanced arsenic methylation and antioxidative capacity was protective against arsenic induced mutagenic DNA breakages and tissue damages.
Asunto(s)
Antioxidantes/metabolismo , Intoxicación por Arsénico/metabolismo , Intoxicación por Arsénico/prevención & control , Arsénico/toxicidad , Daño del ADN , Ácido Fólico/uso terapéutico , Vitamina B 12/uso terapéutico , Vitaminas/uso terapéutico , Animales , Ensayo Cometa , Femenino , Pruebas de Función Renal , Pruebas de Función Hepática , Malondialdehído/metabolismo , Mutágenos/toxicidad , Ratas , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
This study elucidates the protective role of Green tea (Camellia sinensis or CS) against arsenic-induced mutagenic DNA-breakage/intestinal (small) damages in female rats. Intestinal epithelial cells receive ingested arsenic initially. Though, the possibility of damages in this tissue is immense and the therapeutic strategies against this damage are of great concern, reports on either issue are scanty. Our earlier study on arsenic-exposed human unveils a link between carcinogenesis and mutagenic DNA damage. Here, we demonstrate that supplementation of CS-extract (10 mg/mL water) with NaAsO2 (0.6 ppm)/100 g b.w. for 28 days to rats offered a significant protection against arsenic-induced oxidative damages to DNA and intestinal (small) tissues by buttressing antioxidant systems. Necrotic and apoptotic damages and their CS-protection are shown in DNA-fragmentation, comet-assay, and histoarchitecture (hematoxylin and eosin and periodic acid-schiff staining) results. Only arsenic exposure significantly decreased intestinal superoxide dismutase, catalase activities, and level of soluble thiol with a concomitant increase in malondialdehyde/conjugated dienes. Alteration of serum necrotic marker lactate dehydrogenase and the metabolic inflammatory marker c-reactive protein also indicate the impairment may be occurring at transcription and/or cellular signal transduction level. In addition, in situ incubation in rat intestinal loop filled for 24 h with NaAsO2 alone (250 µM) or with aqueous CS-extract (250 mg/mL) suggests that small intestinal epithelial cells are significantly protected by CS against arsenic-associated necrotic/mutagenic damages, which is observed in DNA-breakage studies. In conclusion, besides intensifying endogenous antioxidant system, CS polyphenols also offer a direct role on free radical scavenging activity that is associated to the protection from mutagenic DNA-breakages and prevention of tissue necrosis/carcinogenesis generated by arsenic.
Asunto(s)
Antioxidantes/metabolismo , Arsenitos/toxicidad , Camellia sinensis/química , Fragmentación del ADN/efectos de los fármacos , Intestino Delgado/efectos de los fármacos , Compuestos de Sodio/toxicidad , Animales , Proteína C-Reactiva/análisis , Camellia sinensis/metabolismo , Catalasa/metabolismo , Ensayo Cometa , ADN/química , ADN/metabolismo , Femenino , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Intestino Delgado/metabolismo , Intestino Delgado/patología , L-Lactato Deshidrogenasa/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Polifenoles/química , Polifenoles/farmacología , Ratas , Superóxido Dismutasa/metabolismoRESUMEN
Green tea (Camellia sinensis; CS) strongly reverses/prevents arsenic-induced apoptotic hepatic degeneration/micronecrosis and mutagenic DNA damage in in vitro oxidant stress model and in rat as shown by comet assay and histoarchitecture (HE and PAS staining) results. Earlier, we demonstrated a link between carcinogenesis and impaired antioxidant system-associated mutagenic DNA damage in arsenic-exposed human. In this study, arsenic-induced (0.6 ppm/100 g body weight/day for 28 days) impairment of cytosolic superoxide-dismutase (SOD1), catalase, xanthine-oxidase, thiol, and urate activities/levels led to increase in tissue levels of damaging malondialdehyde, conjugated dienes, serum necrotic-marker lactate-dehydrogenase, and metabolic inflammatory-marker c-reactive protein suggesting dysregulation at the transcriptional/signal-transduction level. These are decisively restrained by CS-extract (≥10 mg/ml aqueous) with a restoration of DNA/tissue structure. The structural/functional impairment of dialyzed and centrifugally concentrated (6-8 kd cutoff) hepatic SOD1 via its important Cys modifications by H2O2/arsenite redox-stress and that protection by CS/2-mercaptoethanol are shown in in vitro/in situ studies paralleling the present Swiss-Model-generated rSOD1 structural data. Here, arsenite(3+) incubation (≥10(-8) µM + 10 mM H2O2, 2 hr) is shown for the first time with this low-concentration to initiate breakage in rat hepatic-DNA in vitro whereas, arsenite/H2O2/UV-radiation does not affect DNA separately. Arsenic initiates Fe and Cu ion-associated free-radical reaction cascade in vivo. Here, 10 µM of Cu(2+)/Fe(3+)/As(3+) +H2O2-induced in vitro DNA fragmentation is prevented by CS (≥1 mg/ml), greater than the prevention of ascorbate or tocopherol or DMSO or their combination. Moreover, CS incubation for various time with differentially and already degraded DNA resulted from pre-incubation in 10 µM As(3+)-H2O2 system markedly recovers broken DNA. Present results decisively suggest for the first time that CS and its mixed polyphenols have potent SOD1 protecting, diverse radical-scavenging and antimutagenic activities furthering to DNA protection/therapy in arsenic-induced tissue necrosis/apoptosis.